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. 2007 Jul;6(1):25-37.
doi: 10.1016/j.cmet.2007.06.005.

The nuclear receptor ERRalpha is required for the bioenergetic and functional adaptation to cardiac pressure overload

Janice M Huss  1 , Ken-ichi Imahashi, Catherine R Dufour, Carla J Weinheimer, Michael Courtois, Atilla Kovacs, Vincent Giguère, Elizabeth Murphy, Daniel P Kelly
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Free article

The nuclear receptor ERRalpha is required for the bioenergetic and functional adaptation to cardiac pressure overload

Janice M Huss et al. Cell Metab. 2007 Jul.
Free article

Abstract

Downregulation and functional deactivation of the transcriptional coactivator PGC-1alpha has been implicated in heart failure pathogenesis. We hypothesized that the estrogen-related receptor alpha (ERRalpha), which recruits PGC-1alpha to metabolic target genes in heart, exerts protective effects in the context of stressors known to cause heart failure. ERRalpha(-/-) mice subjected to left ventricular (LV) pressure overload developed signatures of heart failure including chamber dilatation and reduced LV fractional shortening. (31)P-NMR studies revealed abnormal phosphocreatine depletion in ERRalpha(-/-) hearts subjected to hemodynamic stress, indicative of a defect in ATP reserve. Mitochondrial respiration studies demonstrated reduced maximal ATP synthesis rates in ERRalpha(-/-) hearts. Cardiac ERRalpha target genes involved in energy substrate oxidation, ATP synthesis, and phosphate transfer were downregulated in ERRalpha(-/-) mice at baseline or with pressure overload. These results demonstrate that the nuclear receptor ERRalpha is required for the adaptive bioenergetic response to hemodynamic stressors known to cause heart failure.

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